Antiparasitic composition for the treatment and protection of pets

ABSTRACT

Composition which is useful in particular for the treatment and protection of domestic animals which are infested with parasites or are likely to be infested with them, these compositions comprising, in the form of a ready-to-use solution:  
     a) an insecticidal active substance of formula (I),  
                 
 
     b) a crystallization inhibitor,  
     c) an organic solvent having a dielectric constant of between 10 and 35, preferably of between 20 and 30,  
     d) an organic co-solvent having a boiling point below 100° C., preferably below 80° C., and a dielectric constant of between 10 and 40, preferably of between 20 and 30.

[0001] The present invention relates to a composition for the treatmentand protection of animals which are infested with parasites or likely tobe infested with them.

[0002] More particularly, the aim of the invention is to control andeliminate the parasites which infest pets, and especially cats and dogs.

[0003] Pets are often infested with one or more of the followingparasites:

[0004] cat and dog fleas (Ctenocephalides felis, Ctenocephalides sp. andthe like),

[0005] ticks (Rhipicephalus sp., Ixodes sp., Dermacentor sp., Amblyomasp. and the like)

[0006] galls (Demodex sp., Sarcoptes sp., Otodectes sp. and the like).

[0007] Fleas cause an animal a great deal of stress and are harmful toits health. Moreover, fleas are also vectors of pathogenic agents, suchas dog tapeworm (Dipylidium caninum), and can also attack man.

[0008] Similarly, ticks can also cause an animal stress and be harmfulto its health. They can also be harmful to man. However, the mostserious problem of ticks is that they are the vector of pathogenicagents which may affect the animal as much as man. Among the majordiseases which need to be avoided, mention may be made of borrelioses(Lyme disease caused by Borrelia burgdorferi), babesioses (orpiroplasmoses caused by Babesia sp.) and rickettsioses (also known asRocky Mountain spotted fever). Ticks can also release toxins withparalysing and inflammatory properties, these toxins occasionally beingfatal.

[0009] Lastly, galls are particularly difficult to combat since thereare very few active substances which act on these parasites, and theyrequire frequent treatment.

[0010] Many more or less active and more or less expensive insecticidesexist. However, phenomena of resistance are often associated with theiruse, as is the case, for example, with carbamates, organophosphoruscompounds and pyrethroids.

[0011] Moreover, international patent application WO-A-87/03781 andEuropean patent application EP-A-0,295,117 describe a large family ofN-phenyl-pyrazoles with a very broad spectrum of activity, includingantiparasitic activities.

[0012] The object of the invention is to provide novel antiparasiticcompositions for the treatment and protection of animals, thesecompositions being of great efficacy while at the same time being easyto use.

[0013] Another object of the invention is to provide such compositionswhich are easy to use on any type of domestic animal, irrespective ofits size and the nature of its coat.

[0014] Yet another object of the invention is to provide suchcompositions which are effective and do not need to be sprinkled overthe animal's entire body.

[0015] Yet another object of the invention is to provide suchcompositions which, when applied locally, will subsequently diffuse overthe animal's entire body and then dry, while at the same time avoidingany phenomenon of crystallization as far as possible.

[0016] Yet another object of the invention is to provide suchcompositions which, after drying, do not affect the appearance of thecoat and in particular do not leave crystals and do not make the coatsticky.

[0017] These objects are achieved by the invention, the subject of whichis antiparasitic compositions which are useful in particular in thetreatment and protection of domestic animals which are infested withparasites or are likely to be infested with them, these compositionscomprising, in the form of a ready-to-use solution:

[0018] a) an insecticidal active substance of formula (I),

[0019]  in which:

[0020] R₁ is a halogen atom, CN or methyl;

[0021] R₂ is S(O)_(n)R₃ or 4,5-dicyanoimidazol-2-yl or haloalkyl;

[0022] R₃ is alkyl or haloalkyl, for example lower haloalkyl;

[0023] R₄ represents a hydrogen or halogen atom; or a radical NR₅R₆,S(O)_(m)R₇, C(O)R₇ or C(O)OR₇, alkyl, haloalkyl or OR₈ or a radical—N═C(R₉)(R₁₀);

[0024] R₅ and R₆ independently represent a hydrogen atom or an alkyl,haloalkyl, C(O)alkyl, S(O)_(r)CF₃, acyl or alkoxycarbonyl radical; or R₅and R₆ may together form a divalent alkylene radical which may beinterrupted by one or two divalent hetero atoms such as oxygen orsulphur;

[0025] R₇ represents an alkyl or haloalkyl radical;

[0026] R₈ represents an alkyl or haloalkyl radical or a hydrogen atom;

[0027] R₉ represents an alkyl radical or a hydrogen atom;

[0028] R₁₀ represents a phenyl or heteroaryl group optionallysubstituted with one or more halogen atoms or groups such as OH,—O-alkyl, —S-alkyl, cyano or alkyl;

[0029] Y represents a halogen atom or a haloalkyl or haloalkoxy radical,for example a lower haloalkoxy radical, or an SF₅ radical, with thepossibility that:

[0030] Y is CN or NO₂ in positions 2 and 6 (with reference to the carbonof the phenyl ring which is attached to the pyrazole ring and designated1);

[0031] the carbon in position 2 of the phenyl ring is replaced by atrivalent nitrogen atom;

[0032] Y is S(O)_(q)CF₃ in position 4 on the phenyl ring, but preferablyhaloalkyl, haloalkoxy or SF₅;

[0033] m, n, q and r represent, independently of each other, an integerequal to 0, 1 or 2;

[0034] p is an integer equal to 1, 2, 3, 4 or 5, preferably equal to 1,2 or 3, in particular 3;

[0035] with the proviso that when R₁ is methyl, then either R₃ ishaloalkyl, R₄ is NH₂, p is 2, Y in position 6 is Cl, Y in position 4 isCF₃ and the carbon in position 2 of the phenyl is replaced by N; or R₂is 4,5-dicyanoimidazol-2-yl, R₄ is Cl, p is 3, Y in position 6 is Cl, Yin position 4 is CF₃ and the carbon in position 2 of the phenyl isreplaced by ═C—Cl,

[0036] it being possible for this compound of formula (I) advantageouslyto be present in the formulation in a proportion of from 1 to 20%,preferably from 5 to 15% (percentages expressed as weight per unitvolume=W/V),

[0037] b) a crystallization inhibitor which is present, in particular,in a proportion of from 1 to 20% (W/V), preferably from 5 to 15%, thisinhibitor satisfying the test according to which:

[0038] 0.3 ml of a solution A comprising 10% (W/V) of the compound offormula (I) in the solvent defined in c) below, and 10% of thisinhibitor, are placed on a glass slide at 20° C. for 24 hours, afterwhich few or no crystals, in particularly fewer than 10 crystals,preferably 0 crystals, are seen with the naked eye on the glass slide,

[0039] c) an organic solvent having a dielectric constant of between 10and 35, preferably of between 20 and 30, the content of this solvent c)in the overall composition preferably representing the complement to100% of the composition,

[0040] d) an organic co-solvent having a boiling point below 100° C.,preferably below 80° C., and having a dielectric constant of between 10and 40, preferably of between 20 and 30; this co-solvent mayadvantageously be present in the composition in a d)/c) weight/weight(W/W) ratio of between 1/15 and 1/2. The solvent is volatile so as toact in particular as a drying promoter, and is miscible with waterand/or with the solvent c).

[0041] Preferably, the insecticidal active substance corresponds toformula (II),

[0042] in which:

[0043] R₁ is a halogen atom, CN or methyl;

[0044] R₂ is S(O)_(n)R₃ or 4,5-dicyanoimidazol-2-yl or haloalkyl;

[0045] R₃ is alkyl or haloalkyl;

[0046] R₄ represents a hydrogen or halogen atom; or a radical NR₅R₆,S(O)_(m)R₇, C(O)R₇ or C(O)OR₇, alkyl, haloalkyl or OR₈ or a radical—N═C(R₉)(R₁₀);

[0047] R₅ and R₆ independently represent a hydrogen atom or an alkyl,haloalkyl, C(O)alkyl, S(O)_(r)CF₃ or alkoxy carbonyl radical; or R₅ andR₆ may together form a divalent alkylene radical which may beinterrupted by one or two divalent hetero atoms such as oxygen orsulphur;

[0048] R₇ represents an alkyl or haloalkyl radical;

[0049] R₈ represents an alkyl or haloalkyl radical or a hydrogen atom;

[0050] R₉ represents an alkyl radical or a hydrogen atom;

[0051] R₁₀ represents a phenyl or heteroaryl group optionallysubstituted with one or more halogen atoms or groups such as OH,—O-alkyl, —S-alkyl, cyano or alkyl;

[0052] R₁₁ and R₁₂ represent, independently of each other, a hydrogen orhalogen atom and possibly CN or NO₂, but with H or halogen beingpreferred;

[0053] R₁₃ represents a halogen atom or a haloalkyl, haloalkoxy,S(O)_(q)CF₃ or SF₅ group;

[0054] m, n, q and r represent, independently of each other, an integerequal to 0, 1 or 2;

[0055] X represents a trivalent nitrogen atom or a radical C—R₁₂, theother three valencies of the carbon atom forming part of the aromaticring;

[0056] with the proviso that when R₁ is methyl, then either R₃ ishaloalkyl, R₄ is NH_(2,) R₁₁ is Cl, R₁₃ is CF₃ and X is N; or R₂ is4,5-dicyanoimidazol-2-yl, R₄ is Cl, R₁₁ is Cl, R₁₃ is CF₃ and X is═C—Cl.

[0057] The alkyl radicals in the definition of the compounds of formulae(I) and (II) generally comprise from 1 to 6 carbon atoms. The ringformed by the divalent alkylene radical representing R₅ and R₆, alongwith the nitrogen atom to which R₅ and R₆ are attached, is generally a5-, 6- or 7-membered ring.

[0058] As a further preference, R₁ is CN, R₃ is halo-alkyl, R₄ is NH₂,R₁₁ and R₁₂ are, independently of each other, a halogen atom, and R₁₃ isa haloalkyl. Preferably also, X is C—R₁₂.

[0059] A compound (A) of formula (I) which is most particularlypreferred in the invention is 1-[2,6-Cl₂ 4-CF₃ phenyl] 3-CN 4-[SO—CF₃]5-NH₂ pyrazole, whose common name is fipronil.

[0060] The compounds of formula (I) may be prepared according to one orother of the processes described in patent applications WO-A-87/3781,93/6089 and 94/21606 or European patent application EP-A-295,117, or anyother process which falls within the competence of a specialist skilledin the art of chemical synthesis. For the chemical production of theproducts of the invention, a person skilled in the art is considered ashaving at his disposal, inter alia, all of the contents of “ChemicalAbstracts” and of the documents which are cited therein.

[0061] Although this is not preferred, the composition may optionallycomprise water, in particular in a proportion of from 0 to 30% (volumeper unit volume V/V), in particular from 0 to 5%.

[0062] The composition may also comprise an antioxidant intended toinhibit aerial oxidation, this agent being present in particular in aproportion of from 0.005 to 1% (W/V), preferably from 0.01 to 0.05%.

[0063] The compositions according to the invention intended for pets, inparticular cats and dogs, are generally applied by deposition on theskin (“spot on” or “pour on” application); this is generally a localizedapplication to a region with a surface area of less than 10 cm²,especially between 5 and 10 cm², in particular at two points andpreferably localized between the animal's shoulders. After deposition,the composition diffuses, in particular over the animal's entire body,and then dries, without crystallizing or changing the appearance (inparticular absence of any whitish deposit or of any dusty appearance) orthe feel of the coat.

[0064] The compositions according to the invention are particularlyadvantageous on the grounds of their efficacy, their speed of action andthe pleasant appearance of the animal's hair after application anddrying.

[0065] As organic solvent c) which can be used in the invention, mentionmay be made in particular of: acetone, acetonitrile, benzyl alcohol,butyl diglycol, dimethylacetamide, dimethylformamide, dipropylene glycoln-butyl ether, ethanol, isopropanol, methanol, ethylene glycol monoethylether, ethylene glycol monomethyl ether, monomethylacetamide,dipropylene glycol monomethyl ether, liquid polyoxyethylene glycols,propylene glycol, 2-pyrrolidone, in particular N-methylpyrrolidone,diethylene glycol monoethyl ether, ethylene glycol, diethyl phthalate,or a mixture of at least two of these solvents.

[0066] The preferred solvents c) are the glycol ethers, in particulardiethylene glycol monoethyl ether and dipropylene glycol monomethylether.

[0067] As crystallization inhibitor b) which can be used in theinvention, mention may be made in particular of:

[0068] polyvinylpyrrolidone, polyvinyl alcohols, copolymers of vinylacetate and vinylpyrrolidone, polyethylene glycols, benzyl alcohol,mannitol, glycerol, sorbitol, polyoxyethylenated sorbitan esters;lecithin, sodium carboxymethylcellulose; acrylic derivatives such asmethacrylates and the like,

[0069] anionic surfactants such as alkaline stearates, in particularsodium, potassium or ammonium stearate; calcium stearate,triethanolamine stearate; sodium abietate; alkyl sulphates, inparticular sodium lauryl sulphate and sodium cetyl sulphate; sodiumdodecylbenzenesulphonate, sodium dioctylsulphosuccinate; fatty acids, inparticular those derived from coconut oil,

[0070] cationic surfactants such as water-soluble quaternary ammoniumsalts of formula N⁺R′R″R′″R″″Y⁻ in which the radicals R are hydrocarbonradicals, optionally hydroxylated, and Y⁻ is an anion of a strong acidsuch as halide, sulphate and sulphonate anions; cetyltrimethylammoniumbromide is among the cationic surfactants which can be used,

[0071] amine salts of formula N⁺R′R″R′″ in which the radicals R areoptionally hydroxylated hydrocarbon radicals; octadecylaminehydrochloride is among the cationic surfactants which can be used,

[0072] nonionic surfactants such as optionally polyoxyethylenatedsorbitan esters, in particular polysorbate 80, polyoxyethylenated alkylethers; polyethylene glycol stearate, polyoxyethylenated derivatives ofcastor oil, polyglycerol esters, polyoxyethylenated fatty alcohols,polyoxyethylenated fatty acids, copolymers of ethylene oxide andpropylene oxide,

[0073] amphoteric surfactants such as lauryl-substituted betainecompounds,

[0074] or preferably a mixture of at least two of these crystallizationinhibitors.

[0075] In a particularly preferred manner, use will be made of acrystallization inhibitor system, namely the combination of afilm-forming agent of polymer type and a surfactant. These agents willbe chosen in particular from the compounds mentioned as crystallizationinhibitor b).

[0076] Among the film-forming agents of polymer type which areparticularly advantageous, mention may be made of:

[0077] the various grades of polyvinylpyrrolidone,

[0078] polyvinyl alcohols, and

[0079] copolymers of vinyl acetate and vinylpyrrolidone.

[0080] As regards the surfactants, mention will be made mostparticularly of nonionic surfactants, preferably polyoxyethylenatedsorbitan esters and in particular the various grades of polysorbate, forexample polysorbate 80.

[0081] The film-forming agent and the surfactant may in particular beincorporated in similar or identical amounts within the limit of thetotal amounts of crystallization inhibitor which are mentionedelsewhere.

[0082] The system thus made up achieves, in a noteworthy manner, theaims of absence of crystallization on the hair and of maintenance of thecosmetic appearance of the coat, that is to say without a tendency tostick together or to have a sticky appearance, despite highconcentration of active substance.

[0083] As co-solvent d), mention may be made in particular of: absoluteethanol, isopropanol (2-propanol), methanol.

[0084] As antioxidant, standard agents are used in particular, such as:butylated hydroxyanisole, butylated hydroxytoluene, ascorbic acid,sodium metabisulphite, propyl gallate, sodium thiosulphate, a mixture ofnot more than two of these antioxidants.

[0085] The compositions according to the invention are usually preparedby simply mixing the constituents as defined above; advantageously, tobegin with, the active substance is mixed into the main solvent, and theother ingredients or adjuvants are subsequently added.

[0086] The subject of the present invention is also a method for thetreatment and/or protection (preventive care) of animals againstparasites, according to which an effective volume of a compositionaccording to the invention is applied to a limited area of the animal,as is described above. The application is advantageously made at twopoints and/or on the animal's back between the shoulders.

[0087] The aim of the method may be non-therapeutic, when it concernscleaning the animal's hair and skin by eliminating the parasites presentas well as their residues and excreta. The animal thus has a coat whichis pleasant to look at and to feel. This also makes it possible toprevent the establishment of fleas in the house.

[0088] The aim may also be therapeutic when it concerns treating aparasitosis which has pathogenic consequences.

[0089] The volume applied may be about 0.3 to 1 ml, preferably about 0.5ml for cats, and about 0.3 to 3 ml for dogs, depending on the weight ofthe animal.

[0090] The volume of composition applied preferably corresponds to adose of compound of formula (I) of between 0.3 and 60 mg, in particularof between 5 and 15 mg, per kg.

[0091] The examples which follow, which are given without any impliedlimitation, illustrate the invention and show how it may be carried out.

EXAMPLES 1 to 12

[0092] The compositions of Examples 1 to 12 are given in the followingtable: Example No. 1 2 3 4 5 6 7 8 9 10 11 12 Active 10 10 10 10 10 1010 10 10 10 10 10 principle (g) Ethanol cm³ 10 7.5 15 10 10 10 10 7.5 1510 10 10 (g) Polyvinylpyr- 5 5 5 5 5 7.5 5 5 5 5 5 7.5 rolidone (g)polysorbate 80 5 5 5 5 5 5 5 5 5 5 5 5 (g) Butylated 0.02 0.02 0.02 00.02 0 0.02 0.02 0.02 0 0.02 0 hydroxy- anisole (g) Butylated- 0.01 0.010.01 0.01 0.01 0 0.01 0.01 0.01 0.01 0.01 0 hydroxy- toluene (g)Diethylene qs 100 cm³ 0 glycol mono- ethyl ether (cm³) Dipropylene 0 qs100 cm³ glycol mono- methyl ether (cm³)

[0093] By way of example, the volume of diethylene glycol monoethylether represented by qs is about 75 cm³ for the formula of Example 1.

[0094] The following are mixed together, by stirring:

[0095] 10 g of active principle 1-[4-CF₃ 2,6-Cl₂phenyl]3-cyano4-[CF₃—SO-]5-NH₂ pyrazole,

[0096] all of the ethanol,

[0097] 60 cm³ of diethylene glycol monoethyl ether or of dipropyleneglycol monomethyl ether (solvents),

[0098] all of the polyvinylpyrrolidone (Kollidon® 17PF from BASF,Germany),

[0099] all of the polysorbate 80 (Tween® from ICI),

[0100] all of the butylated hydroxyanisole (if present),

[0101] all of the butylated hydroxytoluene (if present).

[0102] The mixture is made up to 100 cm³ with diethylene glycolmonoethyl ether or with dipropylene glycol monomethyl ether (for Example1, this corresponds to a remaining volume of about 15 cm³).

[0103] Each mixture constitutes a concentrated solution S.

[0104] 3 dogs, weighing about 7, 14 and 28 kg respectively, are infestedwith 100 fleas each. Two days later, they are treated by cutaneousapplication of a solution S in a proportion of 0.1 ml/kg, in localizedform over about 5 cm² between the shoulders in the area of the withers.After 24 hours, the time required for complete drying, the appearance ofthe dogs' coat in the area of the deposition on the skin and elsewhereis identical to the initial appearance. In particular, the animal's coatis neither tacky nor sticky when touched and the coat contains nobristled tufts.

[0105] 24 hours after treatment, the dogs are combed in order to removeand count any fleas which may be present. Then, at weekly intervalsafter the treatment, the animals are reinfested in the same way asbefore. 24 hours after each experimental reinfestation, the animals areagain combed in order to remove and count any fleas which may still bepresent. Over a period of 13 weeks, it was observed that there was apercentage reduction in the population of fleas which was maintainedabove 95% when compared with a control group which had not received thetreatment according to the invention.

EXAMPLES 12 to 24

[0106] For Examples 12 to 24, it suffices to replace, in the abovetable, Examples 1 to 12 by 12 to 24 respectively, with 12.5 g of activeprinciple. The amounts of the other constituents are unchanged, apartfrom the amount of solvent required for the complement to 100 cm³.

[0107] The following ingredients are mixed together, by simple stirring:

[0108] 12.5 g of the compound of Example 1

[0109] all of the ethanol

[0110] 60 cm³ of diethylene glycol monoethyl ether or of dipropyleneglycol monomethyl ether

[0111] all of the polyvinylpyrrolidone

[0112] all of the polysorbate 80

[0113] all of the butylated hydroxyanisole (if present)

[0114] all of the butylated hydroxytoluene (if present).

[0115] The mixture is made up to 100 cm³ with diethylene glycolmonoethyl ether or with dipropylene glycol monomethyl ether.

[0116] When used under the conditions described in Example 1, thesemixtures lead to comparable results. A greater than 95% reduction in thepopulation of fleas is observed in less than 24 h when compared with thecontrol group.

1. Composition which is useful in particular for the treatment andprotection of domestic animals which are infested with parasites or arelikely to be infested with them, these compositions comprising, in theform of a ready-to-use solution: a) an insecticidal active substance offormula (I),

 in which: R₁ is a halogen atom, CN or methyl; R₂ is S(O)_(n)R₃ or4,5-dicyanoimidazol-2-yl or haloalkyl; R₃ is alkyl or haloalkyl; R₄represents a hydrogen or halogen atom; or a radical NR₅R₆, S(O)_(m)R₇,C(O)R₇ or C(O)OR₇, alkyl, haloalkyl or OR₈ or a radical —N═C(R₉)(R₁₀);R₅ and R₆ independently represent a hydrogen atom or an alkyl,haloalkyl, C(O)alkyl, S(O)_(r)CF₃, acyl or alkoxycarbonyl radical; or R₅and R₆ may together form a divalent alkylene radical which may beinterrupted by one or two divalent hetero atoms such as oxygen orsulphur; R₇ represents an alkyl or haloalkyl radical; R₈ represents analkyl or haloalkyl radical or a hydrogen atom; R₉ represents an alkylradical or a hydrogen atom; R₁₀ represents a phenyl or heteroaryl groupoptionally substituted with one or more halogen atoms or groups such asOH, —O-alkyl, —S-alkyl, cyano or alkyl; Y represents a halogen atom or ahaloalkyl or haloalkoxy radical, for example a lower haloalkoxy radical,or an SF₅ radical, with the possibility that: Y is CN or NO₂ inpositions 2 and 6 of the phenyl ring; the carbon in position 2 of thephenyl ring is replaced by a trivalent nitrogen atom; Y is S(O)_(q)CF₃in position 4 on the phenyl ring, but preferably haloalkyl, haloalkoxyor SF₅; m, n, q and r represent, independently of each other, an integerequal to 0, 1 or 2; p is an integer equal to 1, 2, 3, 4 or 5, preferablyequal to 1, 2 or 3, in particular 3; with the proviso that when R₁ ismethyl, then either R₃ is haloalkyl, R₄ is NH_(2,) p is 2, Y in position6 is Cl, Y in position 4 is CF₃ and the carbon in position 2 of thephenyl is replaced by N; or R₂ is 4,5-dicyanoimidazol-2-yl, R₄ is Cl, pis 3, Y in position 6 is Cl, Y in position 4 is CF₃ and the carbon inposition 2 of the phenyl is replaced by ═C—Cl, b) a crystallizationinhibitor which satisfies the test according to which: 0.3 ml of asolution A comprising 10% (W/V) of the compound of formula (I) in thesolvent defined in c) below, and 10% of this inhibitor, are placed on aglass slide at 20° C. for 24 hours, after which fewer than 10 crystals,preferably 0 crystals, are seen with the naked eye on the glass slide,c) an organic solvent having a dielectric constant of between 10 and 35,preferably of between 20 and 30, d) an organic co-solvent which is adrying promoter, having a boiling point below 100° C., preferably below80° C., and a dielectric constant of between 10 and 40, preferably ofbetween 20 and
 30. 2. Composition according to claim 1, characterized inthat the compound of formula (I) is present in a proportion of from 1 to20% W/V, preferably from 5 to 15%, in the composition.
 3. Compositionaccording to claim 1, characterized in that the crystallizationinhibitor is present in a proportion of from 1 to 20% W/V, preferablyfrom 5 to 15%, in the composition.
 4. Composition according to claim 1,characterized in that the organic solvent represents the complement to100% of the composition.
 5. Composition according to claim 1,characterized in that the organic co-solvent is present in thecomposition in a co-solvent d)/solvent c) W/W ratio of between 1/15 and1/2.
 6. Composition according to claim 1, characterized in that water ispresent in a proportion of from 0 to 30% V/V, preferably from 0 to 5%,in the composition.
 7. Composition according to claim 1, characterizedin that it comprises an antioxidant.
 8. Composition according to claim7, characterized in that the antioxidant is present in a proportion offrom 0.005 to 1% (W/V), preferably from 0.01 to 0.05%.
 9. Compositionaccording to claim 1, characterized in that the solvent c) is chosenfrom the group consisting of: acetone, acetonitrile, benzyl alcohol,butyl diglycol, dimethylacetamide, dimethylformamide, dipropylene glycoln-butyl ether, ethanol, isopropanol, methanol, ethylene glycol monoethylether, ethylene glycol monomethyl ether, monomethylacetamide,dipropylene glycol monomethyl ether, liquid polyoxyethylene glycols,propylene glycol, 2-pyrrolidone, in particular N-methylpyrrolidone,diethylene glycol monoethyl ether, ethylene glycol, diethyl phthalate,and a mixture of at least two of these solvents.
 10. Compositionaccording to claim 1, characterized in that the crystallizationinhibitor is chosen from the group consisting of: polyvinylpyrrolidone,polyvinyl alcohols, copolymers of vinyl acetate and vinylpyrrolidone,polyethylene glycols, benzyl alcohol, mannitol, glycerol, sorbitol,polyoxyethylenated sorbitan esters; lecithin, sodiumcarboxymethylcellulose; acrylic derivatives such as methacrylates andthe like, anionic surfactants such as alkaline stearates, in particularsodium, potassium or ammonium stearate; calcium stearate,triethanolamine stearate; sodium abietate; alkyl sulphates, inparticular sodium lauryl sulphate and sodium cetyl sulphate; sodiumdodecylbenzenesulphonate, sodium dioctylsulphosuccinate; fatty acids, inparticular those derived from coconut oil, cationic surfactants such aswater-soluble quaternary ammonium salts of formula N⁺R′R″R′″R″″Y⁻ inwhich the radicals R are hydrocarbon radicals, optionally hydroxylated,and Y³¹ is an anion of a strong acid such as halide, sulphate andsulphonate anions; cetyltrimethylammonium bromide, amine salts offormula N⁺R′R″R′″ in which the radicals R are optionally hydroxylatedhydrocarbon radicals; octadecylamine hydrochloride, nonionic surfactantssuch as optionally polyoxyethylenated sorbitan esters, in particularpolysorbate 80, polyoxyethylenated alkyl ethers; polyethylene glycolstearate, polyoxyethylenated derivatives of castor oil, polyglycerolesters, polyoxyethylenated fatty alcohols, polyoxyethylenated fattyacids, copolymers of ethylene oxide and propylene oxide, amphotericsurfactants such as lauryl-substituted betaine compounds, and preferablymixtures of at least two of these crystallization inhibitors. 11.Composition according to claim 1, characterized in that, ascrystallization inhibitor, it comprises a crystallization inhibitorsystem including a polymeric film-forming agent and a surfactant. 12.Composition according to claim 11, characterized in that the polymericfilm-forming agent is chosen from the group consisting of: variousgrades of polyvinylpyrrolidone; polyvinyl alcohols; and copolymers ofvinyl acetate and vinylpyrrolidone.
 13. Composition according to claim11, characterized in that the surfactant is a nonionic surfactant. 14.Composition according to claim 13, characterized in that the surfactantis a polyoxyethylenated sorbitan ester such as polysorbate. 15.Composition according to claim 14, characterized in that thecrystallization inhibitor is a mixture of polyvinylpyrrolidone andpolysorbate, preferably polysorbate
 80. 16. Composition according toclaim 1, characterized in that the solvent c) is a glycol ether. 17.Composition according to claim 16, characterized in that the solvent c)is chosen from the group consisting of diethylene glycol monoethyl etherand dipropylene glycol monomethyl ether.
 18. Composition according toclaim 1, characterized in that the co-solvent d) is chosen from thegroup consisting of: absolute ethanol, isopropanol, methanol. 19.Composition according to claim 1, characterized in that it comprises anantioxidant chosen from the group consisting of: butylatedhydroxyanisole, butylated hydroxytoluene, ascorbic acid, sodiummeta-bisulphite, propyl gallate, sodium thiosulphate and a mixture ofnot more than two of these antioxidants.
 20. Composition according toclaim 1, characterized in that the insecticidal substance corresponds toformula (II):

in which: R₁ is a halogen atom, CN or methyl; R₂ is S(O)_(n)R₃ or4,5-dicyanoimidazol-2-yl or haloalkyl; R₃ is alkyl or haloalkyl; R₄represents a hydrogen or halogen atom; or a radical NR₅R₆, S(O)_(m)R₇,C(O)R₇ or C(O)OR₇, alkyl, haloalkyl or OR₈ or a radical —N═C(R₉)(R₁₀);R₅ and R₆ independently represent a hydrogen atom or an alkyl,haloalkyl, C(O)alkyl, S(O)_(r)CF₃ or alkoxycarbonyl radical; or R₅ andR₆ may together form a divalent alkylene radical which may beinterrupted by one or two divalent hetero atoms such as oxygen orsulphur; R₇ represents an alkyl or haloalkyl radical; R₈ represents analkyl or haloalkyl radical or a hydrogen atom; R₉ represents an alkylradical or a hydrogen atom; R₁₀ represents a phenyl or heteroaryl groupoptionally substituted with one or more halogen atoms or groups such asOH, —O-alkyl, —S-alkyl, cyano or alkyl; R₁₁ and R₁₂ represent,independently of each other, a hydrogen or halogen atom and possibly CNor NO₂, but with H or halogen being preferred; R₁₃ represents a halogenatom or a haloalkyl, haloalkoxy, S(O)_(q)CF₃ or SF₅ group; m, n, q and rrepresent, independently of each other, an integer equal to 0, 1 or 2; Xrepresents a trivalent nitrogen atom or a radical C—R₁₂, the other threevalencies of the carbon atom forming part of the aromatic ring; with theproviso that when R₁ is methyl, then either R₃ is haloalkyl, R₄ is NH₂,R₁₁ is Cl, R₁₃ is CF₃ and X is N; or R₂ is 4,5-dicyanoimidazol-2-yl, R₄is Cl, R₁₁ is Cl, R₁₃ is CF₃ and X is ═C—Cl.
 21. Composition accordingto claim 1, characterized in that the compound of formula (I) is1-[4-CF₃2,6-Cl₂phenyl]3-cyano4-[CF₃—SO]5-NH₂ pyrazole.